Hypoxia – Histotoxic and Anemic hypoxia, Hypercapnia & brain injuries

Opioid receptors in Hypoxia: – 

Opioid receptors in Hypoxia are stimulated by endogenous endorphins, which usually cause analgesia and feelings of well-being. Opioids are used clinically, mainly as analgesics. Opioids differ in their receptor activity, and some (eg, buprenorphine) have combined agonist and antioxidant actions.

Exogenous opioids can be taken by almost any route: orally, intravenously, subcutaneously, internally, through the nasal membrane, or inhaling as smoke. Peak effects reach about 10 minutes after IV injection, 10 to 15 minutes after nasal insufficiency, and 90 to 120 minutes after oral ingestion, although peak effects and duration of effect vary greatly depending on the specific drug it occurs.

 

Histotoxic hypoxia: –

Histotoxic hypoxia (also referred to as histo-toxic hypoxia) is that the inability of cells to require or use oxygen from the bloodstream, despite physically normal delivery of oxygen to such cells and tissues. Histotoxic hypoxia results from tissue poisoning, like cyanide (which works by inhibiting cytochrome oxidase) and a few other toxins like sulfide (a by-product of sewage and tanning of leather).

In histotoxic hypoxia, the cells of the body are unable to use oxygen, although its amount in the blood can be normal and under normal stress. However, manufactured by cyanide, any agent that reduces cellular respiration may be the cause. Some of these agents are narcotics, alcohol, formaldehyde, acetone, and some anesthetic agents.
Drug overdose causes histotoxic hypoxia. As in this case, the drug inactivates the enzyme dehydrogenase, causing tissue oxidation to be inhibited. Thus, the tissue becomes capable of using oxygen.

 

Anemic hypoxia:

In this form of hypoxia, the lungs are in perfect working condition, but the oxygen-carrying capacity of the blood is reduced. As the name itself suggests, anemia is a very effective way of causing anemic hypoxia. Carbon monoxide produces anemic hypoxia – as it binds Hb with such high affinity, preventing oxygen from binding, it reduces the oxygen-carrying capacity of the blood. Tissues do not get enough oxygen to maintain their metabolic needs because the blood is not carrying it. Arterial Po2 is normal but the amount of Hb available to carry O2 is small

Causes: –
1. Anemia
2. Hemorrhage
3. Abnormal Hb– MetHb where iron is in ferric form instead of ferrous form, HbS, COHb, etc
Pathophysiology: –
• Here at rest hypoxia is not severe as in anemia there is more 2,3 DPG which releases o2 from Hb
• During exercise more o2 demand by tissues as more o2 is consumed so severe hypoxia develops
Compensatory Changes: –
1. Hyper dynamic circulation, increased CO and HR
2. Increased speed of blood flow so that the same Hb can be used repeatedly to transport o2.
3. Rise of 2,3 DPG
4. More erythropoiesis due to more EP in an attempt to correct anemia.

Hypercapnia: –

Hypercapnia means excess carbon dioxide in the body fluids. Hypercapnia usually occurs in association with hypoxia only when the hypoxia is caused by hypoventilation or circulatory deficiency. The transport capacity of the blood for carbon dioxide is more than that for oxygen so that the resulting tissue Hypercapnia is much less than the tissue hypoxia. Serious Hypercapnia usually does not occur at the same time because carbon dioxide diffuses 20 times as rapidly as oxygen. If Hypercapnia does begin to occur, this immediately stimulates pulmonary ventilation, which corrects the Hypercapnia but not necessarily the hypoxia.  When the alveolar Pco2 rises above 60 to 75 mm Hg – breathing becomes rapid and deep – “air hunger” – dyspnea becomes severe.

If the Pco2 rises to 80 to 100 mm Hg, the person becomes sluggish and sometimes even semi-comatose. Anesthesia and death can result when the Pco2 rises to 120 to 150 mm Hg.
At higher levels of Pco2, the excess carbon dioxide begins to depress respiration rather than stimulate it, thus causing a vicious circle: (1) more carbon dioxide, (2) further decrease in respiration, (3) then more carbon dioxide, and so forth ending rapidly in a respiratory death
• high alveolar PCO2, which means high arterial PCO2
• you will rarely see one change and the other not change, but you cannot say that about O2 unless you are in a single alveolus (ventilation goes up, O2 goes up, CO2 goes up)
• FCO2 is proportional to PCO2, related by the barometric pressure
• FCO2 is the fraction = PCO2/barometric pressure)
• FACO2 = VCO2/VA
• Normal alveolar ventilation  4200 for someone with total ventilation of 6000 mL/min
• PCO2 = 40 mmHg
• CO2 excretion rate = 200-250 ml/min

MECHANISMS OF HYPERCAPNIA -alveolar hypoventilation • -respiratory failure • -cerebral blood vessels are the most sensitive to CO2, PCO2 • -the adaptive value of increasing blood pressure  brings more blood to the brain • -bring more CO2 to the lungs and attempt to excrete more • -CO2 narcosis – when CO2 is above 80-90 mmHg, decrease ventilation by ½

 

Hypoxic brain injuries

Hypoxic brain injuries:- are brain injuries that form due to a restriction on the oxygen being supplied to the brain. The restricted flow of oxygen causes the gradual death and impairment of brain cells. This type of hypoxia is known as ischemic or stagnant hypoxia in which the blood flow to a tissue is so low that adequate O2 is not delivered to it despite a normal PO2 and hemoglobin concentration. Ischemic hypoxia ( or “stagnant hypoxia”) – Reduced brain oxygen is caused by inadequate blood flow to the brain. Stroke, shock, cardiac arrest, and heart attack may cause stagnant hypoxia. Ischemic hypoxia can also be created by pressure on the brain.

• Due to slow speed of blood flow or stagnation blood stays for long in tissues,
• venous Po2 is less an accumulation of co2 in tissues shifts the curve to right so more o2 is released to tissue

Causes :

1. CCF
2. Circulatory failure
3. Hemorrhage
4. Shock
5. Venous obstruction

Tissue or Histotoxic Hypoxia

Tissue or Histotoxic Hypoxia: – O2 delivered to the tissues is normal but the tissues cannot utilize o2.  hypoxia in tissues: –

• venous PO2 is high and someone who dies of it will look cherry red
• shock=tissue hypoxia
• only purpose of delivering oxygen to the tissue is to make sure there is some oxygen at the end of the electron transport chain
• mitochondrial PO2 is maintained very low so a minor drop in arterial blood wi
ll cause a major drop in mitochondrial
• cyanide can be used as a chemical warfare agent and Met Hb scavenges cyanide and makes cyano-MetHb, removing the cyanide from the blood
• DeoxyHB scavenges nitrous oxide (vasodilator necessary to keep total peripheral resistance normal)
So tissues cannot use o2 so values at the venous end are similar to arterial end.
Causes:
1. Cyanide Poisoning- cyanide blocks the action of cytochrome oxidase enzyme completely so tissues cannot utilize o2.
2. Vitamin B def or Beri Beri where also several important steps of o2 utilization are blocked.